DESCRIPTION (Scanned from the Applicant's Description): It was previously unclear how unconscious increases in energy expenditure (EE) in the face of increased energy consumption could act to prevent fat gain. We carefully measured energy storage and changes in EE in response to overfeeding and determined that increases in non-exercise activity thermogenesis (NEAT) predicted (r=0.78, p<0.001) resistance to fat gain in non-obese subjects. In this application we intend to further investigate NEAT. We first propose to identify the principal components of NEAT in free-living lean volunteers. Our hypothesis is that ambulating EE accounts for the majority of NEAT in free-living subjects. We will combine portable inclinometers and accelerometers and laboratory measurements of EE to quantify the EE of lying, sitting, standing and walking in the free-living state. By summation, we will predict NEAT. A measurement of 'fidgeting' will also be obtained using accelerometer data. Total NEAT will be measured in free-living subjects using doubly labeled water to assess total daily EE (TDEE) combined with laboratory measurements of RMR and TEF; NEAT = TDEE - (BMR + TEF). We will thereby be able to ascertain whether walking EE or other components of NEAT or 'fidgeting' best predict NEAT in free-living subjects. Second, to determine whether obesity is associated with an inability to activate NEAT in response to overeating, we will overfeed obese subjects, weight-stable post-obese and lean controls and measure the changes in NEAT. Our hypothesis is that obesity represents a state of reduced ability to activate NEAT with overfeeding. If the components by which NEAT mediates resistance to fat gain can be discerned, this might provide insight into the mechanism by which NEAT mediates resistance to weight gain with over-feeding. In addition, these studies may provide information regarding the pathogenesis of obesity and potentially into novel modalities for preventing and treating obesity.